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B Group Vitamins - Current Research on Their Role in Human Health [Working Title]
Open access peer-reviewed chapter - ONLINE FIRST
B-Group Vitamin-Producing Lactic Acid Bacteria: A One Health Approach to Improving Human and Companion Animal Health
Written By
Romina Levit, Natalia Carrasco, Martin Nicolas Cerasuolo,
Paola Alexandra Yanez, Fatima Nader de Macias,
Alejandra De Moreno De LeBlanc and Jean Guy LeBlanc
Submitted: 27 February 2026Reviewed: 25 May 2026Published: 02 September 2026
It has been shown that specific strains of lactic acid bacteria (LAB) have the capacity to produce and/or deliver vitamins such as, folates, riboflavin, thiamin, and cobalamin. In addition, LAB have been extensively used as probiotics since specific strains have been shown to provide health benefits to consumers. In this chapter, we will discuss the current research available demonstrating that vitamin-producing LAB can provide health benefits in humans and companion animals. Their role in the prevention or treatment of inflammatory intestinal diseases, neurological disorders, and certain types of cancers will be reviewed. In addition, taking into account the One Health concept of the WHO, the use of vitamin-producing bacteria will also be analyzed in relation to the health of household pets, as these can have a direct impact on their owners’ health.
Centro de Referencia para Lactobacilos (CERELA-CONICET-FML-FECIC), San Miguel de Tucumán, Argentina
Natalia Carrasco
Centro de Referencia para Lactobacilos (CERELA-CONICET-FML-FECIC), San Miguel de Tucumán, Argentina
Martin Nicolas Cerasuolo
Centro de Referencia para Lactobacilos (CERELA-CONICET-FML-FECIC), San Miguel de Tucumán, Argentina
Paola Alexandra Yanez
Centro de Referencia para Lactobacilos (CERELA-CONICET-FML-FECIC), San Miguel de Tucumán, Argentina
Fatima Nader de Macias
Centro de Referencia para Lactobacilos (CERELA-CONICET-FML-FECIC), San Miguel de Tucumán, Argentina
Alejandra De Moreno De LeBlanc
*
Centro de Referencia para Lactobacilos (CERELA-CONICET-FML-FECIC), San Miguel de Tucumán, Argentina
Jean Guy LeBlanc
Centro de Referencia para Lactobacilos (CERELA-CONICET-FML-FECIC), San Miguel de Tucumán, Argentina
*Address all correspondence to: leblanc@cerela.org.ar
1. Introduction
Vitamins are micronutrients required for the metabolism of living organisms. These compounds have highly specific functions and are, therefore, normally not required in large quantities, unlike other types of nutrients. Vitamins are categorized into two groups: fat-soluble (vitamins A, D, E, and K) and water-soluble (vitamin C and B-group vitamins: thiamin (B1), folate (B9), pyridoxine (B6), niacin (B3), pantothenic acid (B5), biotin (B7), riboflavin (B2), and cobalamin (B12)) [1].
Humans do not have the ability to synthesize vitamins (except vitamin D), and therefore, they must incorporate them from exogenous sources such as, diet or supplements. Although vitamin requirements can be obtained within a balanced diet, there are many cases of deficiencies throughout the world. This is why several countries have adopted food fortification laws [2]. Currently, bioenriched foods are emerging as an alternative to fortification with chemically synthesized vitamins, and the use of vitamin-producing microorganisms appears as an interesting biotechnological strategy due to its economic and environmentally friendly advantages [3]. Specifically, some strains of lactic acid bacteria (LAB) can synthesize natural forms of certain vitamins, such as, riboflavin, folate, thiamine, and cobalamin, which are not associated with the adverse effects of the chemical forms [4].
Lactic acid bacteria are a group of Gram-positive microorganisms that can ferment carbohydrates and produce numerous metabolites of interest to the food industry. Lactic acid bacteria have been used in the fermentation of different types of food as starter cultures, since through this process the flavor of the food can be improved, the nutritional value increased, and the shelf life extended [2]. Furthermore, LAB have been extensively studied and have gained relevance due to their ability to produce bioactive compounds with health-related benefits during fermentation processes. Among these metabolites are vitamins with antioxidant/antiinflammatory effects, bioactive peptides with antihypertensive effects, bacteriocins with antimicrobial activity, and exopolysaccharides with cholesterol-lowering and antidiabetic properties [5, 6].
1.1 Riboflavin production by LAB
Riboflavin (vitamin B2) is an essential component of cellular metabolism; it is the precursor of two coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which act by mediating electron transfer in oxidation–reduction reactions [7].
In adults, the European Food Safety Authority (EFSA) recommends a daily intake of 1.6 mg for both men and women, increasing to 1.9 mg and 2 mg during pregnancy and lactation, respectively [8]. While this vitamin is present in foods such as, leafy green vegetables, cereals, dairy products, eggs, and meat, deficiencies exist primarily in developing countries due to insufficient consumption, but also in developed countries due to dietary changes (veganism, lactose intolerance, etc.) [9]. These deficiencies often have a variety of associated problems, including inflammation of the skin and mucous membranes, circulatory and vision problems, liver damage and neurological dysfunction, impaired glucose metabolism, and anemia [10].
Riboflavin has been produced by total chemical synthesis and semi-chemical synthesis, but its microbial production has also been studied, mainly in both Gram-positive and Gram-negative bacteria (Bacillus subtilis and Escherichia coli), as well as in filamentous fungi and yeasts (Ashbya gossypii and Candida famata) [11]. Currently, the use of genetically engineered bacteria offers advantages over other strategies, such as, shorter production cycles, the use of simple raw materials, high yields, and lower production costs. The most recent advances are related to the application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR/Cas9) genome editing techniques in B. subtilis and A. gossypii [12].
In recent years, different strains of LAB have been studied for their ability to produce this vitamin. A large number of wild-type strains have been isolated from different food matrices (dairy products, cereals) and have demonstrated the ability to produce riboflavin. The riboflavin biosynthesis pathway in LAB has recently been reviewed in detail [13]. It was even possible to increase production levels of the vitamin by using overproducing phenotypes, such as, roseoflavin-resistant strains or recombinant strains that can confer the ability to produce riboflavin to nonproducing strains. However, the use of genetically modified strains is limited for application in human foods [14, 15].
1.2 Folate production by LAB
Folate (vitamin B9) refers to a compound formed by a pteridine ring, para-aminobenzoic acid (PABA), and glutamate. Folate can exist in different forms depending on the oxidation level of the pteridine ring: if it is fully oxidized, it is called folic acid; if it is partially reduced, it is called dihydrofolate; and if it is completely reduced, it is known as tetrahydrofolate [16]. It is worth noting that these are related compounds that exhibit similar biological activity, acting primarily as cofactors for metabolic enzymes in the transport of one-carbon units during DNA synthesis and methylation, as well as the synthesis of amino acids and nucleotides [2].
The recommended daily intake for folate is 400 µg in adults and 600 µg in pregnant women, and this micronutrient can be found in a variety of foods such as, leafy green vegetables, some fruits, legumes, dairy products, and cereals [17]. However, in many countries, both developed and developing, consumption is insufficient, and it has been observed that a deficiency of this vitamin can be related to the appearance of different problems, such as, neural tube defects, megaloblastic anemia, neurodegenerative disorders, cardiovascular disease, increased risk of breast and colorectal cancer, among others [18]. Because folic acid deficiency became a global concern, many countries decided to fortify certain foods, such as, flour, milk, or rice, with folic acid on an industrial scale to ensure adequate consumption among their populations. The United States and Canada were the first to do so, establishing mandatory fortification between 1996 and 1998. Some Central and South American countries followed suit in the 2000s. Australia then implemented fortification in 2009, and finally, the European Union and China established voluntary fortification programs between 2006 and 2012, respectively. While these policies are having a positive impact on public health, with a decrease in the number of births with neural tube defects, some studies have shown that high folic acid consumption is associated with adverse effects, such as, masking of vitamin B12 deficiency and linking it to various types of cancer [19, 20].
An alternative to fortifying foods with synthetic folic acid is the biofortification using LAB that are able to produce the natural forms of the vitamin and increase its content in foods [21]. Several studies have documented that fermentation with LAB increased folate levels in both dairy products (milk and yogurt) and nondairy products (oats, barley, and sourdough for bakery products) [14, 22]. Various genera capable of producing folate both intracellularly and extracellularly have been described, this being a strain-dependent property. The folate (vitamin B9) biosynthesis pathway in LAB has recently been reviewed in detail [23]. In addition, different factors or culture conditions that can affect vitamin production (presence of precursors, pH, temperature, etc.) have also been studied [2, 21]. While most bacteria have metabolic regulatory mechanisms that allow them to control folate levels – that is, to produce the metabolite when needed and stop production when the required level is reached – similar to the case of riboflavin, folate – overproducing strains have been obtained using different techniques. For example, mutants resistant to analogs or genetic engineering techniques that allow the overexpression of genes involved in the biosynthesis of the vitamin or other related metabolites, as well as the inactivation of certain undesirable genes. These techniques also made it possible to transform a strain with a plasmid containing the folate gene cluster and convert auxotrophic strains into producers [16].
1.3 Thiamine production by LAB
In addition to riboflavin and folate, LAB has shown potential to produce other B vitamins such as, thiamine and cobalamin.
Thiamine, or vitamin B1, plays an essential role as a cofactor for enzymes involved in carbohydrate metabolism to provide energy. It is also important for the proper functioning of the nervous system, acting as a neuromodulator by promoting acetylcholine neurotransmission and helping to maintain the integrity of cell membranes in neurons and neuroglia [24, 25].
A daily intake of 1.1 mg is recommended for adults, and thiamine can be found in foods such as, whole grains, legumes, nuts, and meat (mainly pork) [26]. Insufficient thiamine intake results in a deficiency that has been linked to the development of pathologies such as, beriberi, cardiovascular diseases, and neurodegenerative diseases such as, Parkinson’s and Alzheimer’s [27].
In addition to plant and animal sources of thiamine, microorganisms can also synthesize the vitamin. In this regard, it is known that certain bacterial phyla present in the intestine have the enzymatic machinery to synthesize free thiamine and its active form, thiamine diphosphate (TDP), and provide the human body with 2.8% of the daily requirement [24, 28]. Furthermore, although there are few studies on this topic, it has been shown that certain strains of LAB increase the levels of vitamin B1 in thiamine-free media [25, 29] and during the fermentation of certain foods (milk, soy) [30].
1.4 Cobalamin production by LAB
Cobalamin corresponds to vitamin B12 and comprises a group of structurally similar compounds formed by a corrinoid ring and containing a cobalt atom. It can naturally exist in different forms, such as, desoxyadenosylcobalamin (coenzyme B12), methylcobalamin, or pseudocobalamin, and the industrially produced form exists as cyanocobalamin [31]. The most important functions of this vitamin are during hematopoiesis, being essential in the production of red blood cells, and as a coenzyme in processes related to the health of the nervous system [32].
The recommended daily intake for vitamin B12 is between 3.8 and 20.7 µg in adults [17]. This vitamin is known to be produced only by prokaryotes (bacteria and archaea); therefore, it can be present in certain animals because it is produced by bacteria in the intestinal tract. In this sense, humans can obtain the vitamin from animal products such as, meat and eggs, and also from fish [22]. Consuming suboptimal amounts of cobalamin can result in hypovitaminosis and lead to problems in the hematopoietic and neurological systems [33].
Cobalamin has been industrially produced through chemical synthesis and microbial fermentation, the latter being the preferred method due to its lower complexity, lower cost, and reduced environmental impact [34]. Currently, the Gram-negative bacterium Pseudomonas denitrificans is used to produce the vitamin via an aerobic process, and the Gram-positive bacterium Propionibacterium shermanii via an anaerobic process [35]. Additionally, the potential of a few strains of LAB to produce cobalamin in vitamin-free media has been reported, some of which have also been evaluated in in vivo models, showing the ability to reverse vitamin B12 deficiency [31]. These bacteria have also been used to increase cobalamin levels in certain foods, such as, soymilk and sourdough [22]. The vitamin B12 biosynthesis pathway in LAB has previously been reviewed in detail [36]. Similar to the other cases mentioned above, it has been possible to increase the production of cobalamin through mutagenesis and genetic engineering techniques, such as the use of plasmids containing the genes for vitamin production [30].
1.5 B-group vitamin-producing LAB: Effects on human and animal health
In recent decades, interest in studying the probiotic potential of LAB has grown, as they have demonstrated beneficial effects for a variety of conditions, such as, inflammatory bowel diseases (IBD), diabetes, allergies, cancer, etc. [37]. This interest has focused on developing both functional foods and therapeutic products containing these bacteria [38]. The definition of a probiotic refers to microorganisms that are live and confer a health benefit to the consumer when administered in adequate amounts [39]. It is known that the positive health effects on a host are specific to each LAB strain, and these microorganisms can act through different mechanisms of action, such as, modulating the gut microbiota, improving barrier function, and stimulating the immune system [40]. In recent years, a new mechanism of action for LAB has been proposed: the supply of vitamins with antioxidant and/or antiinflammatory activity. In this way, B-group vitamin-producing LAB could provide a dual benefit, both nutritional and therapeutic, and the latter may be due to the effects of the vitamin itself as well as those of the bacterial strain [41].
This chapter will review the findings published over the last two decades describing the beneficial effects of LAB associated with their production of B vitamins. This review will focus on three different pathologies: intestinal inflammation, cancer, and neurodegenerative diseases. Finally, under the One Health approach, it will also review published data on how these bacteria may affect the health of companion animals.
A comprehensive literature search was conducted across the PubMed, SciELO, ResearchGate, and Google Scholar databases. The search strategy employed keywords such as, probiotic, LAB, B vitamin, riboflavin, folates, and thiamine. For each section, specific keywords were added: inflammation, IBD, mucositis, cancer, chemotherapy, neurodegeneration, and Parkinson. Peer-reviewed articles published in English and Spanish during the last two decades were included. The selection criteria prioritized empirical studies and systematic reviews describing randomized clinical trials, human studies, and preclinical studies, while excluding editorials and conference abstracts.
Inflammatory bowel diseases are a group of chronic disorders affecting the gastrointestinal tract. The pathogenesis of these diseases is multifactorial and influenced by an individual’s genetic predisposition (presence or mutation of certain genes) and environmental factors (diet, smoking, antibiotic use, etc.), as well as by a dysregulated immune response and an imbalance in the gut microbiota (decreased microbial variability) [42]. There are two main clinical types: ulcerative colitis (UC), characterized by continuous inflammation of the mucosal layer in the rectum and colon, and Crohn’s disease (CD), which presents with discontinuous transmural lesions in any portion of the gastrointestinal tract [43].
The pharmacological treatments currently used to treat symptoms and help patients achieve remission include antibiotics, immunomodulators, corticosteroids, biologics, and aminosalicylics. However, these treatments have the disadvantage of being only partially effective due to variability in patient responses, and they also have associated adverse effects when used for extended periods [44].
A characteristic feature of patients with IBD is that they also have nutritional deficiencies. This can be due to insufficient food intake caused by discomfort or restrictive diets, as well as absorption problems and/or nutrient losses related to altered intestinal epithelial integrity. These deficiencies can involve macro and micronutrients, mainly vitamins and minerals [45]. On the other hand, there are several studies in which vitamin supplementation has been associated with beneficial effects against IBD in both animal models and human studies. This was the case for vitamin A [46], vitamin C [47], and vitamin E [48]. Furthermore, vitamin D deficiency has been linked to a higher probability of developing IBD [49]. Regarding B vitamins and their effect on IBD, an antiinflammatory effect of pyridoxine has been reported [50]. Positive effects of thiamine, riboflavin, and cyanocobalamin have also been observed in experimental models of colitis [51, 52], but there are few studies on this topic.
Considering the antioxidant/antiinflammatory effects that some B – group vitamins have demonstrated, LAB capable of producing these vitamins have also been evaluated in experimental models of IBD. A study evaluated a riboflavin-overproducing strain, Lactiplantibacillus (L.) plantarum CRL2130, in a murine model of colitis. Mice receiving both the strain in soymilk and the bacterial suspension showed improvements in intestinal inflammation parameters, including decreased weight loss, less damage to the large intestine, reduced microbial translocation to extraintestinal organs such as, the liver, and decreased levels of proinflammatory cytokines in intestinal fluids. Furthermore, the antioxidant potential of the riboflavin-overproducing strain was also confirmed through in vitro experiments [53, 54]. Additionally, the administration of a bacterial mixture consisting of the aforementioned riboflavin-overproducing strain L. plantarum CRL2130, a folate-producing strain Streptococcus (S.) thermophilus CRL808, and an immunomodulatory strain S. thermophilus CRL807 was studied as an adjuvant to an antiinflammatory drug (mesalazine) in a murine model of chronic colitis. In that study, it was observed that the bacterial blend was able to attenuate the side effects of the drug, such as, weight loss and some intestinal damage, without affecting its activity [55]. Other studies have shown the positive effects of cobalamin-producing strains in an experimental model of colitis, including a decrease in colonic shortening and a reduction in the disease activity index (DAI) [56]. In addition, similar effects were also reported for folate-producing strains in the same model [57]. In another study, three strains of Pediococcus (P.) acidilactici were isolated from human fecal samples, in which the genes for vitamin B2 and B9 production were identified and then evaluated in a rat colitis model. The results showed an improvement in colon histology and in antiinflammatory and antioxidant biomarkers in the animals that received these bacteria [58]. The administration of a cobalamin-producing Lactobacillus strain isolated from canines was also studied in mice with colitis, and a preventive/therapeutic effect was observed. This effect was related to a decrease in the expression of proinflammatory cytokines in the colon, as well as lower myeloperoxidase activity and malondialdehyde levels [59].
2.2 Intestinal mucositis
Intestinal mucositis (IM) is defined as the structural and functional damage to the intestinal mucosa that occurs as a side effect of treatments used in cancer patients [60]. Antineoplastic therapies, such as, chemotherapy and radiotherapy, use drugs or radiation to destroy cancer cells; however, these treatments cannot discriminate between tumor cells and healthy cells, so the effect is on all rapidly proliferating cells indiscriminately [61]. Intestinal mucositis is a pathology that constitutes a serious problem, as it not only affects patients’ quality of life but also, in many cases, leads to the discontinuation of cancer treatments [62].
Intestinal mucositis develops in several stages; first, radiotherapy and chemotherapy damage the DNA of epithelial cells with the generation of reactive oxygen species (ROS), followed by the activation of transcription factors such as Nuclear Factor-kappa B (NF-κB), which are involved in the expression of inflammatory molecules. Then, there is a stage of inflammation amplification, followed by apoptosis, cell loss, and even ulceration. Finally, there is a stage of reepithelialization, restructuring, and restoration of intestinal function [63].
Currently, there are no treatments for IM, only some preventive or palliative strategies for the symptoms (abdominal pain and diarrhea), such as, antidiarrheal agents, antiinflammatories, analgesics, cryotherapy, antibiotics, and mucosal coatings [64, 65].
The structural alterations that occur in the intestinal epithelium (apoptosis, villous atrophy, crypt hypoplasia, etc.) during IM lead to functional alterations, such as, impaired fluid and nutrient absorption, resulting in malnutrition in patients. For this reason, nutritional supplements or megavitamin therapy are frequently prescribed [62, 66, 67]. On the other hand, different studies have shown the positive effects of fat-soluble vitamins, such as, vitamins A, D, and E [67–71], as well as water-soluble vitamins, such as, vitamins B2, B9, and C [72, 73] against chemotherapy-induced IM in both preclinical models and human studies. These studies used different chemotherapeutic drugs, such as, irinotecan, cisplatin, 5-fluorouracil (5-FU), or methotrexate, to induce the disease, and it was observed that the administration of the aforementioned vitamins had positive effects, such as improvement in anorexia, onset of diarrhea, and weight loss; less intestinal damage; suppression of the inflammatory response; modulation of oxidative stress; and prevention of mucin depletion [74].
Given that the pathogenesis of IM involves the production of ROS and the activation of the immune response, new therapeutic approaches with antioxidant/antiinflammatory activity are being explored. In this regard, vitamin-producing LAB have been evaluated in experimental models of this pathology. A previous study evaluated a riboflavin-overproducing strain, L. plantarum CRL2130, in a murine model of IM induced with 5-FU. The results showed beneficial effects in animals, such as, decreased weight loss, less diarrhea, reduced histological damage in the small intestine, and an antiinflammatory profile measured in cytokines from intestinal fluid and/or serum [75]. Subsequent studies evaluated a folate-producing strain, S. thermophilus CRL808, in the same model, and the results were equally beneficial. Furthermore, it was confirmed through in vitro assays that none of the evaluated bacteria affected the activity of the anticancer drug [76]. These two bacteria were combined with a third one selected for its immunomodulatory activity, S. thermophilus CRL807, and were evaluated in an in vivo model of breast cancer under chemotherapy treatment with 5-FU. The results showed a greater antiinflammatory effect from the bacterial mixture than from administering the individual strains, confirming that these bacteria could be a good adjuvant to cancer therapies in order to reduce unwanted side effects [77].
These studies highlight the potential of vitamin-producing LAB in the prevention/treatment of IBD and IM, as they can modulate inflammation, reverse nutritional deficiencies in patients, and even be used as an adjunct to primary treatments to mitigate undesirable side effects.
Among their mechanisms of action, they have the potential to modulate the host’s immune response, in addition to exerting antioxidant effects described for certain B vitamins, and the potential to modulate the gut microbiota, which is known to be imbalanced in these pathologies (Figure 1). Regarding clinical studies, while clinical trials exist with general probiotics in IBD, the literature lacks specific studies using strains selected for their high production of B vitamins. This makes this field a developing area, considering the results obtained in preclinical studies and the history of benefits and safety associated with LAB.
Figure 1.
Schematic representation of the antiinflammatory mechanisms described in the literature by which lactic acid bacteria that produce B vitamins (folate, riboflavin, and cobalamin) can exert benefits in in vitro and in vivo models of intestinal inflammation (mucositis, colitis).
3. B vitamins in cancer biology: Metabolism, homeostasis, and clinical implications
The relationship between B vitamins and cancer is complex, as each vitamin plays a crucial role in the body’s cellular biology. These molecules participate in fundamental biological processes such as, metabolism and the management of genetic information. Therefore, the action of vitamins in the body is associated with blocking the onset and progression of cancer [78, 79]. In this regard, abnormal serum levels of B vitamins, both high and low, have been detected and linked to the development of cancer. Some vitamins, such as, B2, B9, B6, and B12, when obtained through diet, have been shown to reduce the risk of colon cancer [80, 81]. However, high intakes of some vitamins, such as folate, have been linked to an increased incidence of cervical cancer [82]. High consumption of vitamin B6 was associated with a reduced risk of pancreatic cancer but increased the risk of lung cancer [83, 84]. It is clear that this complex relationship between vitamins and cancer requires in-depth studies on the specific type of cancer being analyzed and the role that each vitamin plays in the context of human health.
Vitamin B2, or riboflavin, is recognized for its antioxidant activity, which stems from its role as a cofactor for enzymes involved in oxidation–reduction processes within the cell [85]. It acts as a precursor to the coenzymes FAD and FMN, which are closely linked to various types of cancer and their therapies. Riboflavin indirectly regulates levels of ROS, which increase due to the use of chemotherapeutic drugs, protecting healthy cells from tissue damage [86–88]. In addition to its antioxidant effect, riboflavin has been shown to modulate the immune system at several key points. For example, it participates in the activation of phagocytosis and the proliferation of macrophages and neutrophils, demonstrating its importance in innate immunity [89]. Additionally, in vitro assays have shown that it can decrease tumor cell migration and reduce the expression of molecules that diminish the cytotoxic effect of CD8+ T lymphocytes, such as Programmed Cell Death Ligand 1 (PD-L1) [90]. In vivo assays have demonstrated that riboflavin truncates liver cancer progression by decreasing the expression of antiapoptotic genes and increasing the expression of proapoptotic genes in tumor cells [91]. Furthermore, riboflavin intake in mice with melanoma has been shown to decrease metastatic invasion into the lungs [92]. These effects observed through experimentation could be the reason why a deficiency of this vitamin is associated with a higher risk of developing cancer.
Vitamin B6 is also known as pyridoxine, and due to the high number of pathways where this vitamin is involved, its relationship with cancer is rather complicated. Some data show that increased intakes of this vitamin could reduce the risk of having cancer in multiple sites, such as, the breast, prostate, cervix, liver, brain, and others [93]. Participation in amino acid metabolism is a key factor in understanding the importance of this vitamin in the context of cancer, especially for solid tumors that have a high demand for amino acids. It also has the capacity to modulate oxidative stress. Pyridoxal 5’-phosphate, a derivative of vitamin B6, was assessed in several studies, leading to the discovery that high concentrations of this molecule are related to lower risks of cancer and reduced cancer development in different types of cancer [94–96]. Overall, studies suggest that a low intake of pyridoxine augments the risk of cancer, while higher levels tend to have a protective effect.
Folate, or vitamin B9, plays an active role in one-carbon metabolism, a biochemical pathway involving other B vitamins along with methionine and homocysteine. The products of this pathway participate in various cellular processes, such as, purine and pyrimidine synthesis, energy production, and several biosynthetic processes. Tumor cells are known to require high levels of folate for constant division, raising questions about the appropriateness of using vitamin B9 as a supplement in these cases. Furthermore, folate deficiency in the body reduces glutathione levels, a molecule with significant antioxidant activity that protects the body from harmful oxidative stress [97]. The drop in glutathione levels triggers a general oxidative state that ultimately leads to DNA damage. At the immunological level, folate deficiency has been shown to impair the stimulation of CD8+ T lymphocytes [98]. Vitamin B9 participates in the S-adenosylmethionine synthesis pathway, which implies that folate is related to the expression of many genes, since S-adenosylmethionine is involved in DNA and RNA methylation. A folate deficiency can lead to DNA breakage and destabilization, as well as inadequate DNA repair [90, 99]. Therefore, both excess and deficiency of folate play an important role in cancer progression. In this sense, Pieroth et al. (2018) emphasized the importance of other nutrients, in addition to folates, being involved in one-carbon metabolism, which leads to the need to analyze the fundamental role of synergy between nutrients, showing that perhaps this could clarify some issues of the dual effect observed for this vitamin [100]. Similar to folate, cobalamin, or vitamin B12, participates in one-carbon metabolism [97]. This indicates that cobalamin is also important in the process of gene expression through methylation of DNA, proteins, and histones. Additionally, this vitamin participates in DNA and RNA repair and replication, which marks it as an important molecule in preventing cancer. On the other hand, an excess of vitamin B12 could increase tumor formation and accelerate cell division. Some studies showed that high cobalamin intakes for prolonged periods of time were associated with higher risks of developing cancer [101]. Also, some population studies showed a positive correlation between high circulating levels of cobalamin in blood samples and higher risks of developing cancer [102, 103].
3.1 Breast cancer and B vitamins
Breast cancer is one of the most frequently diagnosed cancers, and its incidence is estimated to be increasing globally [104, 105]. There is conflicting evidence regarding the relationship between this disease and B vitamins. It is known that one of the most common genetic mutations in the development of breast cancer occurs in the BRCA genes, which encode proteins that repair DNA. Supplementation with folate and vitamin B12 has been shown to have protective effects against these types of cancer [106]. In the case of folate, high plasma levels have also been shown to inhibit breast cancer invasion and proliferation, as well as prevent metastasis [107]. It has been reported that the administration of vitamin complexes that include vitamins B2, B6, B9, and B12 could be related to a decrease in the incidence of breast cancer, especially the estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor type 2-positive types [78]. Similarly, the intake of these vitamins (except B12) has been associated with lower incidences of estrogen receptor-negative and progesterone receptor-negative cancers [79]. It has also been observed that the type of breast cancer at the molecular level is related to the effect of high serum concentrations of vitamins B9 and B12. In some cases, it was associated with a higher risk of developing certain types of breast cancer, while in other types of breast cancer, at the molecular level, no relationship was found with serum levels of these vitamins [108, 109]. Some human studies showed that vitamins B1 and B5 were elevated in patients with benign breast tumors or cancer compared to healthy individuals, while vitamin B3 was low in both healthy individuals and those with benign tumors. Additionally, it was observed that serum concentrations of some vitamins changed if patients were being treated with chemotherapy drugs [110].
3.1.1 The influence of microbiota on B vitamins and cancer
In recent years, the gut microbiota has been described as an important source of B vitamins. Although the number of vitamins produced by the microorganisms inhabiting the gut is not sufficient to meet the host’s entire needs, their contribution to the body is substantial. It is known that the ability to produce these compounds depends on the phylogenetic groups to which microorganisms belong. It is estimated that between 20% and 25% of the microorganisms found in the human gut are auxotrophic for vitamins B1, B2, B3, B5, and B9, while these values increase for vitamins B7 and B12 [111]. This reinforces the theory that, within this microbiome, bacteria interact to compensate for potential vitamin deficiencies in microorganisms unable to produce them themselves. The most widely accepted theory to explain how these vitamins reach the host is that these molecules are synthesized within microbial cells and released into the environment through cell lysis.
The functions performed by the gut microbiota have a significant impact on the body. Medication intake, diet, inflammation, or stress can induce changes in gut microbiota, affecting the host’s homeostasis [112]. An imbalance in the gut microbiota, called dysbiosis, triggers the appearance of various pathologies, and cancer is no exception [113].
Although it might initially be assumed that dysbiosis only involves the appearance of abnormalities in tissues adjacent to the intestinal microbiota, that is cancers of the digestive tract, it has been shown that the effects of dysbiosis are much broader, even influencing the appearance of tumors in distant sites of the intestine [114]. Recent studies on the relationship between the gut microbiota and cancer have described a bidirectional influence between them [115]. The gut microbiota can produce effects that promote or suppress tumor development, making the study of the composition of these microbial populations extremely important [116, 117]. Dysbiosis produces an increase in the abundance of pathogenic species, which negatively impact the host’s health, triggering tumor development both in the intestinal tract and in distal sites of the organism [118, 119]. In contrast, the antitumor effects of the gut microbiota are closely linked to the production of certain metabolites by them, such as short-chain fatty acids [120, 121]. Another molecule involved in antitumor activity is lipopolysaccharides (LPS) from Gram-negative bacteria, which binds to Toll-like receptors (TLR)4 receptors, triggering the activation of CD8+ T lymphocytes that participate in antitumor immunity. Furthermore, some bacteria can confer health benefits to the host through protective effects against dysbiosis or by boosting immune defenses [115, 116].
In addition, it is important to consider that chemotherapy is still used as an effective treatment against metastatic cancers, including breast cancer [122], but it carries a lot of side effects. Among these, inflammation of the digestive tract is a problematic concern due to its implications for the normal functionality of the gut and has been described as the trigger point of dysbiosis in cancer patients, diminishing the abundance of microorganisms involved in the metabolism of vitamins and other metabolic pathways [123, 124]. This is counterproductive when it comes to preventing tumor progression, as already described.
Due to the positive effects exhibited by the microorganisms of the gut microbiota, the use of probiotics as promoters of healthy states in the organism and as prevention agents of dysbiosis has been studied more extensively in recent years. The positive effects associated with the consumption of probiotics have been described against many different diseases, including cancer. It has been reported that probiotics in cancer studies served as prevention and mitigation of negative side-effects associated with chemotherapy, emphasizing the protection of gut microbiota from the dysbiosis caused by the mentioned treatments [125]. Though promising, it is important to consider that patients receiving chemotherapy and/or radiotherapy are immunosuppressed and, therefore, safety studies need to be performed before administering living microorganisms to them [126]. On the other hand, the effects of probiotics depend on the specific strains used, and different mechanisms were associated with the anticancer effects of probiotics. Additionally, a strategy to revert the B vitamin deficiencies caused by the use of chemotherapeutic drugs, by administering specific strains with the capacity to produce B vitamins, becomes a feasible strategy to overcome complications of breast cancer [127]. The research evaluated the effect of a mixture of three LAB, including a riboflavin-producer, a folate-producer, and an immunomodulatory strain, as a coadjuvant for 5-FU chemotherapy in a 4T1 cells-induced breast cancer model. The bacterial mixture reduced the side-effects associated with chemotherapy without interfering with its primary antitumor activity. In addition, these bacteria showed an antitumor effect by themselves, which opened the opportunity for future studies of vitamin-producing LAB against cancer. The benefits of these strains in fighting the tumor, together with mitigating the negative side-effects of therapies and providing essential nutrients (vitamins), could improve the quality of life of cancer patients and potentially extend their life expectancy.
Given the context of the multifaceted effects of B vitamins on tumor biology, future investigation is required to establish optimal intakes of these molecules in order to identify specific factors for each patient and to achieve safe, nutritional, and deliverable interventions in the prevention and treatment of cancer. Lactic acid bacteria are also emerging as a strategy for obtaining natural forms of vitamins, which, in some cases, differ from the chemical forms included in dietary supplements (such as folic acid) and are metabolized differently. Therefore, demonstrating whether these forms are safer for cancer patients highlights the need for further research. Figure 2 summarizes the limited results found in the literature using in vitro and in vivo models, which allow us to describe the potential of vitamin B-producing LAB against cancer.
Figure 2.
Schematic representation of the mechanisms described in the literature by which vitamin B-producing lactic acid bacteria (folate, riboflavin) can exert benefits against different types of cancer and their chemotherapy treatments.
4. B-group vitamins and probiotics against neurodegenerative disorders and aging
The rate of global population aging continues to increase each year as a consequence of advances in medicine; however, the gap between life expectancy and healthy life expectancy results in a large proportion of older adults living with chronic diseases. Among these, neurodegenerative diseases have shown one of the greatest increases, with Alzheimer’s and Parkinson’s being the most common dementias in the adult population, driven by aging-associated processes such as, protein aggregation, inflammation, and oxidative stress.
These disorders are also associated with deficiencies in B-group vitamins, which are essential for neuronal function. Their bioavailability may be compromised by alterations in the gut microbiota, positioning probiotic bacteria capable of producing these vitamins as a promising strategy against neurodegeneration.
In this context, the objective of this section is to analyze the role of the microbiota–gut–brain axis in the relationship between B-group vitamin deficiencies, alterations in the gut microbiota, and the potential of vitamin-producing probiotic bacteria as a strategy against neurodegeneration.
4.1 Etiology and pathophysiological mechanisms of neurodegenerative diseases
The etiology of neurodegenerative diseases is complex and multifactorial, influenced by genetic, environmental, and metabolic factors. It is characterized by the progressive loss of selectively vulnerable neuronal populations, leading to progressive neuronal dysfunction and ultimately cell death [128]. Among the most prevalent neurodegenerative diseases are Alzheimer’s disease (AD) and Parkinson’s disease (PD).
Environmental factors associated with an increased risk of developing these disorders include exposure to environmental toxins, such as, heavy metals and pesticides, which may trigger cellular alterations that promote neurodegeneration. Genetic predispositions also constitute a determining factor in disease onset. In this regard, specific mutations have been identified, such as, those associated with the apolipoprotein E (APOE) gene in AD and the leucine-rich repeat kinase 2 (LRRK2) gene in PD, which significantly increase susceptibility to these conditions [129, 130].
Multiple pathophysiological mechanisms collectively contribute to the progression of neurodegeneration, including misfolded protein aggregation, oxidative stress, activation of apoptotic pathways, and neuroinflammation [128]. Protein misfolding and aggregation constitute one of the most relevant pathological mechanisms in these disorders. In this process, specific proteins adopt abnormal conformations that promote their aggregation and accumulation both intracellularly and extracellularly, disrupting essential cellular processes such as, synaptic function, axonal transport, and protein degradation systems.
Additionally, these pathological proteins have been shown to induce the misfolding of neighboring proteins through prion-like mechanisms, helping to explain the characteristic anatomical distribution of neuropathological lesions. This aggregation process is associated with mitochondrial dysfunction and the activation of apoptotic pathways, culminating in progressive neuronal loss [131, 132].
Oxidative stress represents another central mechanism in the pathophysiology of neurodegenerative diseases. The brain is particularly vulnerable to this type of damage due to its high metabolic demand and limited antioxidant capacity. In this context, increased levels of reactive oxygen and nitrogen species cause damage to nucleic acids, proteins, and lipids, triggering apoptotic pathways and contributing to neuronal dysfunction. Oxidative damage is closely linked to mitochondrial dysfunction, establishing a vicious cycle that amplifies cellular injury [133].
Finally, neuroinflammation constitutes a key mechanism in the progression of neurodegeneration. Microglia and astrocytes are the primary cells responsible for the inflammatory response in the central nervous system. Although this response initially serves a protective function, its persistent activation leads to the release of proinflammatory cytokines, chemokines, and ROS, promoting synaptic dysfunction and neuronal death [134, 135].
4.2 B-group vitamins: Metabolism and neuronal function in aging
Another fundamental factor during aging is the adequate metabolism of B-group vitamins, which is essential for maintaining neuronal and cognitive function. Vitamins B12 and B6 are critical for the normal functioning of the adult nervous system, and low intakes of vitamin B12 and folate have been associated with neuropsychiatric disorders [136].
B-group vitamins are water-soluble and participate in fundamental metabolic processes, including energy production, DNA and RNA synthesis and repair, genomic and nongenomic methylation, and the synthesis of neurochemicals. In particular, the coenzymes pyridoxine (B6), folate (B9), and cobalamin (B12) play an indispensable role in the methylation of homocysteine to methionine, a process critical for proper nervous system function [137].
Deficiency of these vitamins leads to elevated homocysteine levels, which promote oxidative stress, excitotoxicity, and microangiopathy [138]. Collectively, B-group vitamins are essential for both catabolic and anabolic metabolism, acting as coenzymes in numerous processes vital to cellular physiology, including brain and nervous system function. Their alterations contribute to increased vulnerability to neurodegenerative processes [139].
4.2.1 Gastrointestinal changes associated with aging and the bioavailability of B-group vitamins
The gastrointestinal tract, together with the gut microbiota it harbors, performs essential functions in maintaining the intestinal barrier, digestion, nutrient absorption, and communication with other organs. However, during aging, the gastrointestinal tract undergoes various physiological modifications that affect appetite control, oral function, intestinal mucosal integrity, motility, and nutrient digestion and absorption [140, 141].
These physiological alterations contribute to the high prevalence of vitamin deficiencies – particularly of the B-complex – in older adults, as aging reduces the absorption of several micronutrients, including vitamin D, calcium, and vitamin B12. Absorption of the latter depends on pepsin activity and gastric acid secretions, which are reduced in this population. Vitamin B12 participates in neurotransmitter synthesis and myelin formation through its influence on nucleic acid synthesis and methylation. Similarly, folate is involved in one-carbon metabolism, regulating key processes such as, nucleotide synthesis and DNA methylation, which are fundamental for homeostasis and proper nervous system function. Vitamin B6 acts as a coenzyme in essential reactions for the synthesis of neurotransmitters – including serotonin, dopamine, norepinephrine, and glycine – playing a central role in neurotransmission and neuronal protection mechanisms [142, 143].
Numerous studies have demonstrated that low levels of B-group vitamins, together with elevated blood homocysteine concentrations, are strongly associated with the presence and severity of neurodegenerative diseases. In this context, supplementation with these vitamins in older adults may contribute to improved cognitive function [141, 144].
Among modifiable risk factors, nutrition has emerged as a promising target for preserving and potentially enhancing cognitive function, particularly through the adequate intake of B-group vitamins, whose optimization may help alleviate cognitive alterations in both older adults and patients with neurodegenerative diseases.
These intestinal alterations have direct implications for brain function through the microbiota–gut–brain axis.
4.3 Microbiota–gut–brain axis
The microbiota–gut–brain axis is a highly complex, bidirectional network that connects the gastrointestinal tract with the central nervous system via a “highway” known as the vagus nerve. The vagus nerve transmits sensory, immunological, and metabolic information between the gut and the brain in both directions [145].
Within this axis, the gut microbiota plays a fundamental modulatory role, as it produces a wide variety of metabolites and bioactive molecules that directly influence neuronal, immune, and endocrine signaling. Among these metabolites are short-chain fatty acids such as, butyrate, propionate, acetate, and valerate, which regulate physiological intestinal processes – including motility, secretion, and inflammatory responses – thereby contributing to intestinal and systemic homeostasis [146–148].
Bidirectional communication within the microbiota–gut–brain axis is further reinforced by the production of neurotransmitters by both host cells and the gut microbiota itself. Key neurotransmitters involved in this system include serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid (GABA) [149, 150]. Approximately 90% of the body’s serotonin is synthesized by enteroendocrine cells in the intestine, where it plays a key role in regulating intestinal motility. Moreover, this neurotransmitter significantly influences mood and cognitive functions at the central level, reinforcing the functional link between the gut and the central nervous system [151].
Gut bacteria also release structural components such as, LPS and peptidoglycans, which act as potent immunological signals through interaction with TLRs. Under physiological conditions, the intestinal barrier restricts the passage of these molecules into systemic circulation. However, when barrier integrity is compromised, these molecules may reach the central nervous system, activate microglia, and promote neuroinflammatory processes associated with the development and progression of various neurological disorders [152, 153].
4.3.1 Intestinal dysbiosis and its contribution to neurodegeneration
Intestinal dysbiosis is defined as an alteration or imbalance in the composition, structure, and function of intestinal microbial communities, resulting from both external and host-related factors [154]. Major contributing factors include alcohol consumption, exposure to additives and contaminants, chronic stress, medication use – especially antibiotics – unhealthy diets, and the sequelae of bacterial or viral infections and gastrointestinal surgeries [155].
In dysbiosis, disruption of the microbial metabolic profile is characterized by increased production of neuroactive microbial metabolites with proinflammatory and prooxidant potential – including amino acid derivatives, ammonia, biogenic amines, and secondary bile acids – along with imbalances in short-chain fatty acids and microbially derived neurotransmitters. These mediators act synergistically to disrupt biological barriers, activate systemic immunity, and promote neuroinflammation. In this context, LPS, components of the outer membrane of Gram-negative bacteria, are released in greater amounts during dysbiosis and inflammatory processes. Alteration of the intestinal epithelial barrier facilitates their systemic translocation, increasing intestinal and blood–brain barrier permeability, microglial activation, and neuroinflammation. Sustained exposure to elevated LPS levels has also been associated with the aggregation of neuropathological proteins such as, amyloid-β, tau, and α-synuclein, contributing to neuronal dysfunction and the development of neurodegenerative diseases [156].
Multiple studies have shown that individuals with neurodegenerative diseases exhibit characteristic patterns of intestinal dysbiosis, including a relative increase in bacteria with proinflammatory potential, such as Enterobacteriaceae and Porphyromonas, along with a decrease in protective bacteria, including Faecalibacterium and Prevotella [155, 157]. However, these patterns are not universal and may vary significantly among individuals depending on environmental, dietary, pharmacological, and lifestyle factors, reflecting the complexity and heterogeneity of the interaction between the gut microbiota and neurodegenerative diseases.
4.4 Gut microbiota and probiotics as modulators of vitamin status and neurodegeneration
Like other physiological systems, the gut microbiota is susceptible to age-related changes, undergoing progressive modifications in composition, diversity, and functionality. Although the microbial ecosystem tends to remain relatively stable during adulthood, the transition to older age and the onset of frailty are associated with reduced microbial richness and diversity [158]. In this context, microbial profiles characteristic of a “young” microbiota – enriched in taxa such as, Clostridiales and Bifidobacterium – shift toward an “aged” microbiota frequently dominated by Proteobacteria and pathobionts. This imbalance is associated with reduced microbial biosynthetic capacity, particularly affecting the production and bioavailability of B-group vitamins [159, 160].
Several studies have shown that certain gut bacterial genera linked to B-complex vitamin metabolism exert modulatory and potentially neuroprotective effects in neurodegenerative diseases. In particular, evidence from Mendelian randomization studies suggests that genera such as, Bifidobacterium and Slackia mediate the relationship between B-complex vitamin status and AD risk, being associated with a lower probability of developing the disorder, whereas the UCG-011 group has been associated with increased disease risk [161].
In animal models of PD, intestinal dysbiosis is associated with a reduction in beneficial genera such as, Bifidobacterium and Lactobacillus, promoting neuroinflammation, oxidative stress, and dopaminergic dysfunction [162]. In an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine Parkinson’s model, administration of a mixture of LAB partially reversed intestinal dysbiosis, with a significant increase in the Lactobacillaceae family. This effect was primarily associated with L. plantarum CRL2130, a riboflavin (vitamin B2) overproducing strain, and Streptococcus thermophilus CRL808, a folate (vitamin B9) producer, highlighting the role of B-complex vitamin–producing bacteria in modulating the gut–brain axis [163]. The importance of riboflavin production in the neuroprotective effect of L. plantarum CRL2130 was also described using the same Parkinsonian model [164].
Similarly, in multiple sclerosis, more robust experimental evidence is available. In experimental autoimmune encephalomyelitis models, the administration of these same bacterial genera significantly attenuated clinical disease severity [165].
These findings underscore the role of the gut microbiota beyond direct supplementation, emphasizing its influence on B-complex vitamin bioavailability and the modulation of key processes involved in neurodegeneration.
During aging, genetic, environmental, and nutritional factors increase susceptibility to neurodegenerative diseases. B-group vitamins are essential for neuronal metabolism and function, and their deficiencies are associated with oxidative stress, neuronal dysfunction, and cognitive decline. Age-related changes compromise their absorption and bioavailability, exacerbating these alterations. In this context, the gut microbiota acts as a key modulator of vitamin status and gut–brain communication. Current evidence supports the potential of nutritional and probiotic interventions as complementary strategies against neurodegeneration. Lactic acid bacteria that produce B vitamins are a promising strategy for improving the gut–brain axis by modulating the immune response, enhancing the gut microbiota, and providing essential nutrients (vitamins) that contribute to a neuroprotective effect. Figure 3 summarizes the possible mechanisms described in the current literature, particularly those reported in parkinsonian models.
Figure 3.
Schematic representation of the mechanisms described in the literature by which vitamin B-producing lactic acid bacteria (folate, riboflavin) can exert benefits against neurodegenerative diseases, highlighting the results obtained in in vivo studies of parkinsonism models.
There is a strong interaction between the health of humans, the animals they come into contact with, and environmental factors. These interactions have led the WHO to work on the topic of One Health, where the health of each actor is directly associated with and affects the health of humans, other animals (both breeding and domestic), and the environment. Pets are animals that live in or around the house and are fed and cared for by humans. Until the 1960s, dogs were mainly kept as utility animals, for example, as draft dogs or watch dogs. Today, pet dogs have become an increasingly important part of human life, and most pet owners treat them as members of their family [166]. Pet ownership in households has increased over the years. According to recently published data, 45.5% of American households own dogs, 46% of Europeans own at least one pet, and 21.6% of people in China keep pets [167]. It is frequently stated that one of the reasons pets exist in households without children is because they are increasingly being used as a substitute for having children in a low-fertility society. However, according to a recently published socio-demographic study [168], in more developed countries where marriage, fertility, and mortality rates are low, pets not only could be complements or replacements for children, but they could also be filling the roles of other absent household members, such as, social companions and emotional support for those who, for example, lack partners or siblings. Nowadays, the so-called “Gen Z” is driving a remarkable shift in multi-pet ownership. This generation is also the largest consumer of pet care because they take pet parenting seriously and treat their fur families like an extension of their human family.
Due to the process of domestication and the fact that people and small companion animals share their dietary style and living environment, with similar lifestyle challenges, pathogen risks, and diseases [169], the study of the pets’ microbiome and its relationship to health or disease has been increasing recently [170, 171]. Evidence suggests there are some similarities between dog and human gut microbiota in terms of gene content and response to diet [169, 172]. Moreover, most research addressing the health benefits of pet ownership shows reductions in distress and anxiety, decreases in loneliness and depression, and increases in physical condition, while also assuming a multifaceted role within our society, including serving as guides, therapists, and law enforcement officers [173].
These facts explain the trend of complementing pet foods with supplements containing vitamins, probiotics, and/or different bioactive ingredients not only to balance the microbiota and improve the quality of their life but also to mitigate the health risks for their owners, who share the same environment and activities, thereby decreasing disease spread due to close contact, mainly with children [174, 175].
For the reasons mentioned above and as a result of the emergence and reemergence of diseases, the “One Health” global strategy has become increasingly important [176]. The One Health initiative is a transdisciplinary approach that emphasizes expanding collaborations and partnerships across all aspects of healthcare for humans, animals, and the environment, providing a basis for combating major threats to public health. This concept highlights the importance of veterinarians and human healthcare experts collaborating, considering human, animal, and environmental health simultaneously, and creating interdisciplinary teams to provide holistic care.
Health implications of vitamins and probiotics in pets’ lives: pregnancy, puppies, and adult life.
Vitamins act as cofactors, precursors, and substrates for numerous biological processes. Mammals, specifically dogs, are unable to synthesize vitamins de novo (with the exception of vitamin C) because they lack most of the enzymes involved in their synthesis. Therefore, dietary intake of these vitamins is essential to prevent deficiencies that can have severe, irreversible health consequences [177]. Folate deficiency is related to a higher incidence of coronary heart disease, osteoporosis, birth defects such as, neural tube defects, megaloblastic anemia, and cancer [178, 179]. In general, folate requirements are higher during periods of rapid cell division and growth, such as, throughout pregnancy and the early stages of life [178]. It has been reported that riboflavin deficiency in animals has been implicated in stunted growth, a higher incidence of diarrhea, fertility problems, and neurological and hematological defects [180]. Kalender et al. [181] evaluated plasma folic acid levels during pregnancy in dogs and concluded that B9 levels tend to decrease as pregnancy progresses, which may indicate increased metabolic utilization for fetal development and placental growth, supporting the importance of vitamin supplementation during this stage. A more recent study aimed to compare the frequency of malformations such as cleft lip and/or cleft palate in newborns and to measure blood folic acid levels in bitches during pregnancy, both with and without oral folic acid supplements [182]. The results demonstrate that supplementing with folic acid during gestation increased blood folate levels in pregnant bitches and reduced the occurrence of craniofacial defects in breeds of puppies with a higher genetic predisposition.
On the other side, LAB are well known for their beneficial functions in the host and for the production of various effective metabolites, such as, vitamins and derivatives, and they are the most frequently used microorganisms as probiotics [169, 175]. These reasons have sparked interest in new strategies, such as, incorporating probiotic and vitamin supplements into canine diets. Studies have shown that host-specific probiotics may be better adapted to the host’s environment [183, 184]. Additionally, the strains used for pets’ probiotics must express some beneficial characteristics required for most of the probiotics’ formulas applied to different species, as indicated by scientific organizations and government regulations [185–187].
Several authors reported that LAB can produce natural forms of folates and riboflavin that are easily processed and absorbed by the intestinal epithelium of mammalian cells [188–190]. However, the ability of LAB to synthesize these vitamins is strain-dependent [178, 191]. Riboflavin and folate-producing LAB could be an interesting option to supplement animal diets, as they would release the vitamins in their feed or produce these essential nutrients in the gastrointestinal tract [190]. Supported by these concepts, the main objective of our research group was to isolate and survey the different beneficial properties of LAB strains from mother’s milk and feces of canine puppies and adult dogs, in order to advance the design of a homologous probiotic + vitamin formula that would be beneficial for canine health. In our work, most of the 100 LAB isolates were obtained, identified by phenotypic and genetic methods, and screened for their beneficial properties, such as, adhesion to epithelial cells, degree of hydrophobicity and autoaggregation, and production of inhibitory metabolites [192, 193]. The strains were assayed for their virulence traits, and four of them were selected for sharing some of these characteristics. Fifty-three percent of the isolates produced riboflavin, and 60% of them were found to produce folate [192]. A phase I assay involving the administration of probiotic and placebo capsules is ready to begin. The mechanisms described in the literature by which B-producing lactic acid bacteria (folate, riboflavin) can exert benefits on the health of canines and, within the One Health concept, also provide benefits to host humans and the environment have been illustrated in Figure 4.
Figure 4.
Schematic representation of the mechanisms described in the literature by which B-producing lactic acid bacteria (folate, riboflavin) can exert benefits on the health of canines and, within the One Health concept also provide benefits to host humans and the environment.
Formulas/dietary supplements available in the market.
Supported by the reasons described above, the use of functional foods with demonstrated therapeutic effects for companion animals, in order to improve their health and well-being, is becoming increasingly popular in the veterinary community. This enduring love for pets is mirrored in the pet industry’s financial health, which shows continued growth and resiliency, with total US pet industry expenditures reaching $152 billion in 2024 (https://americanpetproducts.org/news/the-american-pet-products-association-appa-releases-2025-state-of-the-industry-report). A significant disadvantage is that most commercial probiotic strains available for dogs usually neither include the origin of isolation nor the beneficial characteristics of the specific strains, but rather claim general benefits without scientific evidence. Table 1 shows the results obtained from a comprehensive review of recent literature on studies conducted with specific strains and probiotic formulas, highlighting that it includes studies in which the strains were isolated from homologous hosts. The type and characteristics of the protocol/assay applied (in vitro, in vivo, phase I, randomized or clinical trial, number of animals evaluated) and the results obtained are also summarized.
Microorganisms and isolation source
Pharmaceutical form or product
Type and characteristic of the protocol. Clinical target
Dogs treated with nonsteroidal anti-inflammatory drugs (NSAID): randomized, double-blinded, placebo-controlled interventional study
Effect on diarrhea, composition of the fecal microbiota, and/or markers of gastrointestinal inflammation
No significant differences in the frequency of diarrhea or changes in the Damage Index of individual bacterial taxa were observed when comparing dogs given LAB versus placebo.
LAB could be a safe supplement for short-term treatment in NSAID-treated dogs
Beneficial-probiotic strains isolated from homologous hosts, as described in the literature, and commercial formulas available in the market.
The literature searches also yielded studies with promising results, in which potential probiotic strains for dogs were obtained from heterologous hosts. Table 2 summarizes these results, highlighting the type and characteristics of the protocol/assay applied (in vitro, in vivo, phase I, clinical or randomized trial, number of animals evaluated) and the results obtained.
Microorganisms and isolation source
Pharmaceutical form or product
Main objective, type, and characteristics of the protocol. Clinical target
Results
Reference
E. faecium IDCC 2,102
B. lactis IDCC 4,301
Infant feces
Supplemented feed
In vivo assay
Obese beagles (2-4 year)
Fed with a high-fat diet to induce obesity and administered the potential probiotics’strains
Beneficial-probiotic strains isolated from heterologous hosts, as described in the literature for dogs.
The literature searches also revealed articles that did not specify the origin of the bacterial strains used. In this regard, the study by Oba et al. (2025) describes that the use of B. subtilis ATCC PTA-122264 in healthy adult beagle dogs may be a strategy to improve the gut microbiota, resulting in lower abundances of Streptococcus, E. coli, and Blautia in feces, although these changes were not reflected in other parameters studied [201]. Another study highlighted the use of different Lactobacillus strains (L. plantarum CM20-8, L. acidophilus IM10, L. rhamnosus L12-2, L. paracasei KT-5, and L. fermentum CM14-8), administered to dogs individually or as a consortium of strains. The results showed that the formulations were safe and non-pathogenic as additives for use as novel probiotic strains. However, the Lactobacillus strains had no effect on the dogs’ hematology, serum biochemistry, nutritional status, digestive enzyme activity, immunity, body weight, feed intake, or body condition. One possibility is the origin of the strains, although the authors do not discuss this [202]. Finally, there are also studies on commercially available probiotic formulas for use in dogs that do not specify the origin of the strains used (homologous or heterologous). Table 3 summarizes the most relevant articles with these characteristics.
Microorganisms and isolation source
Pharmaceutical form or product
Main objective, type, and characteristics of the protocol. Clinical target
Results
Reference
L. plantarum AMT4 and AMT14 strains, and
B. animalis AMT30
Not available
PetBIOM, Owlie S.A., Vet No. αPL2814117p, Stawiguda, Poland
In vivo assay
Puppies, aged between one and seven days, exhibiting diarrhea
High efficacy in stopping diarrhea
The animals demonstrated expected weight gain and were in good condition.
Probiotic formulas available in the market described in the literature for dogs.
There is limited scientific information on most of the available products in the market, which indicates a strong requirement for clinical assays to demonstrate the claimed effects. Referring to publications on specific strains, some studies report results carried out in “in vitro” protocols using homologous strains. However, as the Food and Agriculture Organization (FAO) recommendations state [187], the claimed probiotic effect must be demonstrated in in vivo assays. Most commercial pet probiotics lack regulatory oversight and evidence-based dosing.
In the case of formulas containing vitamins or promoting their release or production, there is no scientific information available, suggesting again a gap in the area.
According to the requirements of regulatory agencies related to the probiotic recommended dose and intake frequency to be consumed/administered, the indications are that probiotic microorganisms must be viable, active, and administered in high numbers to obtain a positive health effect in the host. For oral supplements, a product must contain at least 107 CFU ml g food at the time of consumption [185].
On the other side, vitamins must be bioavailable, even though there is no universal “recommended daily intake” for each B vitamin in dogs that can be applied to all dogs equally. Rather, recommendations by the Association of American Feed Control Officials (AAFCO) guidelines and the European Pet Food Industry Federation (FEDIAF) are made based on minimum levels per metabolic energy or per amount of food, taking into account size, life stage, and physiological condition. In this subject, several studies reveal how the stability of water-soluble and fat-soluble vitamins can be affected by different factors. Yang et al. [207] selected two different types of commercial enteral formulas to evaluate changes in vitamins at different temperatures and relative humidity over 10 days. The results showed that as temperature or storage time increased, the content of vitamins such as, A, E, and B1 gradually decreased, while others, such as C, remained stable. Vitamins, in general, showed greater stability when stored at 25 ± 1°C and a relative humidity of 60 ± 5%. According to a guide for parenteral nutrition [208], the stability of B vitamins depends on photoprotection, temperature, and storage conditions. Main factors include that the greater stability of folic acid is associated with Polyvinyl chloride (PVC) bags and that vitamin B1 has greater stability in the absence of bisulfites in the amino acid solution. Also, refrigeration provides greater stability to vitamin B12.
For the reasons mentioned above, it is of main importance to take into account the techniques and processes that will be applied to the design and formulation of the pharmaceutical/complementary product. However, until now, there is a lack of information on the stability of certain vitamins, such as those in the B group, as they have been less studied. Therefore, a gap exists in protocols directed at evaluating the effect of probiotic/beneficial strains with individually or combined vitamins, to support their recommended intake and the accuracy of the label statements. Likewise, there is a need to explore their potential application with different bioactive compounds or phytochemicals that have complementary beneficial effects in companion animals. Under the “One Health” approach, caring for the health of household pets benefits everyone. Probiotics are key allies in this endeavor, and among them, LAB that produce B vitamins, if properly selected, have the potential to strengthen your pet’s immunity and well-being, while also providing essential nutrients. In this regard, keeping pets healthy, in turn, protects the health of the entire household.
While there are studies in which LAB were genetically modified to produce higher concentrations of vitamins, these were not included in this chapter due to the lack of regulations regarding the use of these microorganisms. However, it is a promising strategy in which the engineering of LAB strains can allow for the development of “vitamin super-producers” strains with a greater capacity to synthesize specific B vitamins at therapeutic levels. It is also very important that future studies demonstrate that the effects attributed to vitamin-producing LAB are indeed associated with vitamin production. In this case, genetics can be a useful tool for silencing vitamin-producing genes and evaluating the resulting strains. Another limitation is ensuring that the microorganisms effectively reach the host; in this regard, innovative formulations such as, encapsulation can serve as a strategy to protect against environmental and digestive stress, ensuring stable and targeted release.
Finally, the trend toward personalized combinations of probiotics and vitamins, based on the unique microbiome profile and needs of each individual, while also taking into account other nutritional contributions, promises a new era of research. These advances could be very important for the “One Health” approach, optimizing overall well-being in all species.
In this chapter, it was demonstrated that B vitamins are essential for various aspects of human health, such as, preventing intestinal, inflammatory, and neurological diseases, as well as certain types of cancer. However, particularly in the latter case, results are contradictory, and further specific studies are needed. Regarding these controversies, one approach is to use natural sources of vitamins, especially folate, instead of synthetic forms, and LAB emerge as an alternative for this purpose. Several articles included in this chapter have shown that B vitamin intake can be improved by using vitamin-producing LAB, either to increase vitamin concentrations in fermented foods or as live carriers for vitamin delivery to the gastrointestinal tract. In addition to producing vitamins in their natural forms, administering certain strains of LAB can also provide additional benefits to the host. Thus, the selection of vitamin-producing strains has shown promising results for improving conventional disease treatments or mitigating the undesirable side effects of prolonged treatments, and this was not solely associated with the provision of vitamins as nutrients. Different mechanisms of action were linked to the beneficial effects of these LAB, including antioxidant effects, modulation of the immune response, and beneficial changes in the gut microbiota, to name a few.
Finally, considering the importance of companion animal health, the use of different probiotics for them was analyzed. The results showed that this is a growing field of study, lacking specific data on the microorganisms used, and one in which vitamin B-producing LAB could be evaluated. The appropriate selection of bacteria with these characteristics, intended for animals to improve their health, will, in turn, beneficially affect the health of people who come into contact with them.
Although there are not enough studies showing the use of LAB that produce B vitamins, the results described in the literature with these microorganisms offer a novel approach to improving health and preventing or treating various diseases.
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Written By
Romina Levit, Natalia Carrasco, Martin Nicolas Cerasuolo,
Paola Alexandra Yanez, Fatima Nader de Macias,
Alejandra De Moreno De LeBlanc and Jean Guy LeBlanc
Submitted: 27 February 2026Reviewed: 25 May 2026Published: 02 September 2026
Open access peer-reviewed chapter - ONLINE FIRST
